Uterine Sarcoma Treatment (Professional) (cont.)
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Stage IV Uterine Sarcoma
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
There is currently no standard therapy for patients with stage IV disease. These patients should be entered into an ongoing clinical trial.
Carcinosarcomas (the preferred designation by the World Health Organization [WHO]) are also referred to as mixed mesodermal or mullerian tumors. Controversy exists about the following issues:
The stromal components of the carcinosarcomas are further characterized by whether they contain homologous elements (such as malignant mesenchymal tissue considered possibly native to the uterus) or heterologous elements (such as striated muscle, cartilage, or bone, which is foreign to the uterus). Carcinosarcomas parallel endometrial cancer in its postmenopausal predominance and in other of its epidemiologic features; increasingly, the treatment of carcinosarcomas is becoming similar to combined modality approaches for endometrial adenocarcinomas.
Patients who present with uterine sarcoma have been treated on a series of phase II studies by the Gynecologic Oncology Group including the GOG-87B trial, for example . These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in patients with carcinosarcomas, a 33% response rate in patients with endometrial stromal cell sarcomas,, and a 17.2% partial response rate in patients with leiomyosarcomas. Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for advanced disease.[5,6] Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas, but cisplatin is inactive as first- or second-line therapy for patients with leiomyosarcomas.[1,7]
A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[Level of evidence: 1iiA] The follow-up GOG-161 study utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4). The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.49–0.97).[Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV uterine sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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